Those who suffer are the beings of the six realms, which are the six possible ways of experiencing samsara (the cycle of rebirth, existence unliberated from suffering).

Beings experiencing the hell realms suffer from intense and unremitting heat or cold, and beings experiencing the hungry ghost realm are constantly deprived of food and drink; these beings of the most unfortunate realms must endure their extreme torment for unimaginable lengths of time without actually dying, until the negative karma that brought about such existences is exhausted.

In the animal realm, beings suffer particularly from ignorance or stupidity and are unable to relate their suffering to others. Beings existing in the human realm experience a mixture of happiness and sorrow as a result of having accumulated both positive and negative karma.

The sufferings of human beings include: birth, sickness, old age, and death; the suffering of being separated from that which one loves, and of not being separated from that which one hates; and the suffering of not getting what one wants and of getting what one does not want.

Beings of the demigod realm are more fortunate, but they suffer because of quarreling, fighting, and warfare. The most pleasant existence is that of the gods, who do not experience suffering until the last seven days of their lives. Then they see signs that the end of their life of ease is approaching; they are abandoned by their attendants, their magnificent bodies deteriorate and their beautiful complexions fade. Finally, they foresee the pain of their next rebirth in the lower realms, which they are bound to experience because their positive karma has been used up.

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Thus, there is no existence in the cycle of samsara that is free from suffering. There are six realms because there are six poisons, or defilements of the mind (Skt. klesha; Tib. nyon-mongs) that are the seeds or causes of the experience of the various realms. There are no more than six realms because there are no more than six poisons to act as seeds. The six poisons are:

1. hatred, or anger, which creates the experience of the hell realm;
2. greed, or miserliness, which creates the hungry ghost realm;
3. ignorance of how to act virtuously is the cause of rebirth in the animal realm;
4. attachment (virtuous action performed with attachment to the meritorious results) is the cause of human rebirth;
5. jealousy (virtuous action sullied by jealousy) causes rebirth in the demigod realm; and
6. pride, or egotism (virtuous action performed with pride) causes a godly rebirth.

The defilements lead to unskillful actions, which generate karma, the infallible operation of cause and effect in the mental continuum of each individual. The negative karma caused by the defilements is the origin of the sufferings of the six realms. The only way to eliminate suffering is to practice the path, method or remedy that will remove the defilements and the negative karma that they produce.

By developing loving-kindness and compassion it is possible to diminish the defilements, but in order to uproot them completely, it is necessary also to develop the discriminating awareness (Skt. prajna; Tib. she-rab) that arises from the wisdom of emptiness. The development of loving-kindness together with wisdom is the result of following the path of Dharma, otherwise known as the five paths: path of accumulation, path of unification, path of seeing, path of meditation, and path of no learning.